AimsTo examine associations of the gut microbial metabolite trimethylamine-N-oxide (TMAO) and its precursors with risk of cardiovascular events in acute coronary syndrome (ACS), and determine whether these associations were mediated by renal function.MethodsIn this prospective cohort study, we included 309 patients with ACS. During a mean follow-up of 6.7 years, 131 patients developed major adverse cardiovascular events (MACE) (myocardial infarction, hospitalization for heart failure, and all-cause mortality). Plasma concentrations of TMAO, trimethylamine (TMA), choline, betaine, dimethylglycine and L-carnitine were profiled by liquid chromatography tandem mass spectrometry. Hazard ratios were estimated with multivariable Cox regression models. The mediating role of estimated glomerular filtration rate (eGFR) was tested under a counterfactual framework.ResultsAfter adjustment for traditional cardiovascular risk factors and medications, participants in the highest tertile vs. the lowest tertile of baseline TMAO and dimethylglycine concentrations had a higher risk of MACE [(HR: 1.83; 95% CI: 1.08, 3.09) and (HR: 2.26; 95% CI: 1.17, 3.99), respectively]. However, with regards to TMAO these associations were no longer significant, whereas for dimethylglycine, the associations were attenuated after additional adjustment for eGFR. eGFR mediated the associations of TMAO (58%) and dimethylglycine (32%) with MACE incidence. The associations between dimethylglycine and incident MACE were confirmed in an internal validation. No significant associations were found for TMA, choline, betaine and L-carnitine.ConclusionThese findings suggest that renal function may be a key mediator in the association of plasma TMAO with the development of cardiovascular events after ACS. The present findings also support a role of dimethylglycine in the pathogenesis of MACE, which may be mediated, at least partially, by renal function.
BackgroundIn this study, we aimed to evaluate the health-related quality of life (HRQL) in patients with severe coronavirus disease 2019 (COVID-19) six months after their hospitalization and compare it to that of nonhospitalized patients with mild COVID-19 and healthy controls.
MethodologyParticipants were enrolled between September 2021 and April 2022 and included hospitalized COVID-19 patients at General Hospital of Athens "Hippocration" who had been discharged at least six months prior to enrollment, non-hospitalized patients with COVID-19, and healthy controls. Collected data included demographics, disease severity, medication history, and comorbidities. Participants completed a EuroQol 5 Dimensions 5Levels (EQ5D5L), a Short Form 36 version 2 (SF36v2), a Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and a Post-COVID-19 Functional Status Scale (PCFSS) regarding HRQL before and six months after infection with severe acute respiratory syndrome coronavirus 2. In the case of healthy controls, two sets of questionnaires were completed at least six months apart. Statistical analysis was performed using the SPSS version 25 software (IBM Corp., Armonk, NY, USA).
ResultsA total of 151 participants were enrolled. Hospitalized patients with COVID-19 demonstrated a statistically significant deterioration in most parameters of SF36v2 as well as both parameters of the EQ5D5L and FACIT-F questionnaires. Hospitalized patients exhibited worse results in SF36v2 and EQ5D5L when compared to both healthy controls as well as those with mild COVID-19 (p < 0.05). Hospitalized women, in particular, were shown to fare worse than other women in parameters associated with both mental/psychological and physical health (p < 0.05). Hospitalized patients between 41 and 60 years old demonstrated a statistically significant drop in the scores of all three main questionnaires compared to their previous health status (p < 0.05). Hospitalized patients between 61 and 80 years old exhibited a similar trend, but statistical significance was achieved in fewer parameters. HRQL decline was greater in both age groups compared to that of healthy and milder disease counterparts. There was a significant correlation between the results from the three main questionnaires. Similarly, PCFS scale values were shown to correlate with disease severity (hospitalization or not) and age.
ConclusionsHRQL remained noticeably impacted six months after hospitalization due to COVID-19. The physical and mental/psychological stress of severe COVID-19 translated into lasting health deterioration, especially for women and those aged 41-60 years old. The use of questionnaires, such as those implemented in this study, might help in the early detection of patients who could benefit from rehabilitation programs. Psychological, as well as physical and social, support is crucial to alleviate the burden of post-COVID-19 symptomatology and expedite the recovery of this group of patients.
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